Anorexia Nervosa (AN) is a serious psychiatric illness for which prognostic factors remain unclear, no effective pharmacotherapy is established, and rates of relapse are high. Elevated levels of physical activity (PA) have long been noted in patients with AN and are considered by some a fundamental feature of the disorder. Physical activity is known to play a critical role in other disorders of weight regulation and evidence suggests that high-level PA is a risk factor for relapse in some patients with AN. However, PA is often surprisingly overlooked in research on AN, possibly because it has been difficult to measure. There has been no systematic attempt to characterize the behavioral and motivational manifestations of PA in AN, and there has been no definitive assessment of the effect of PA on clinical outcome. These are critical questions for a disorder in which clarification of the phenotype(s), pathophysiology, and prognostic factors may prove essential to advancing its treatment. The overarching goals of this R01 grant proposal are to characterize PA and its role in the outcome of patients with AN. To do so we propose a comprehensive, multidimensional assessment employing cutting-edge approaches translated from two related fields of research. Specific Aims are to (1) Apply a novel device employed in metabolism research, the IDEEA, in conjunction with accelerometry, to characterize PA in AN qualitatively and quantitatively; and (2) Apply the Progressive Ratio (PR) task, used extensively in behavioral economics and addictions research, to quantify the reinforcing effect of exercise in patients with AN, and (3) Determine the ability of measures obtained under Aims 1 and 2 to predict one-year outcome following inpatient treatment with weight restoration for AN. Collaborators will include experts in research on metabolism and behavioral economics and addictions. Anticipated dividends of this work include identification of behavioral phenotype(s) of AN with distinct treatment needs, and of physiological and behavioral targets for such treatment. PUBLIC HEALTH RELEVANCE: Anorexia Nervosa is a serious psychiatric disorder of self-starvation, in which physical activity levels are sometimes extremely elevated. This proposed project will apply novel translational measurements to determine the nature of physical activity and its role in the outcome of Anorexia Nervosa. Results may improve our ability to predict prognosis in Anorexia Nervosa and may lead to development of more effective treatments for this disorder.